This project, called also The Diabetes Autoimmunity Study in the Young (DAISY), began in July 1993 and allowed the investigators to establish two unique cohorts of very young children who are at increased (up to 20-fold) risk of insulin-dependent diabetes mellitus (IDDM): (i) a cohort of nearly 300 siblings and offspring, aged initially 0-7 years, relatives of persons with IDDM, and (ii) a cohort of approximately 500 newborns with IDDM associated HLA-DR, DQ alleles, identified through a cord blood screening of 10,000 general population children without a relative with IDDM. In the next 5 years, the investigators are proposing: 1. to continue the follow-up of the sibling/offspring cohort until the mean age of 10 yrs, and of the general population newborn cohort until the mean age of 6 yrs, to further define the natural history of beta-cell autoimmunity, and to sustain this population laboratory for additional studies of IDDM and other autoimmune diseases; 2. to complete, with sufficient power, already initiated studies of dietary and viral determinants of beta-cell autoimmunity and its persistence; 3. to develop automated reliable high-throughput methods, using dried blood blots, to screen for the following: a) the HLA-DRB1*03/*04, DQB1*0302 genotype that is present in 2% of the general population, but in 35-50% of IDDM children, b) autoantibodies against beta-cell antigens GAD65, ICA512 (IA-2), and phogrin; and 4. using these high-throughput methods: a) to screen an estimated 50,000 Colorado newborns for the high risk HLA-DRB1*03/*04, DQB1*0302 genotype, and b) to enroll 780 of an estimated 1,170 eligible high risk children in a prospective follow-up, similar to that already underway, with assessment of selected environmental exposures and yearly screening for beta-cell autoantibodies. The investigators point out that the study is filling an important gap in the understanding of the events leading to IDDM. They further state that the proposed follow-up of this large high risk population will likely bring more complete understanding of IDDM cases and prevention opportunities.